tbuckley/cabot-search huggingface dataset:
Effect of Apatinib Plus Pegylated Liposomal Doxorubicin vs Pegylated Liposomal Doxorubicin Alone on Platinum-Resistant Recurrent Ovarian Cancer
Authors: Tiantian Wang, Jie Tang, Hongying Yang, Rutie Yin, Jingru Zhang, Qi Zhou, Ziling Liu, Lanqin Cao, Li Li, Yi Huang, Kui Jiang, Wei Wang, Fenglin She, Ni Guan, Zhiguo Hou, Ning Li, Lingying Wu
Journal: JAMA Oncology (2022)

There are substantial unmet therapeutic needs in patients with platinum-resistant recurrent ovarian cancer (PROC), and novel therapeutic strategies should be explored.To evaluate the efficacy and safety of treatment with apatinib (a vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor) plus pegylated liposomal doxorubicin (PLD) for PROC.The APPROVE trial was performed as an open-label, randomized clinical trial at 11 hospitals in China between March 22, 2018, and November 16, 2020. Patients with histologically confirmed ovarian cancer who had experienced disease progression during or within 6 months of discontinuing any prior line of treatment with platinum-based chemotherapy were eligible. This primary analysis was based on data that were current as of January 28, 2021.Patients received PLD alone (40 mg/m2, intravenously, every 4 weeks, for up to 6 cycles) or PLD plus apatinib (250 mg, orally, daily).The primary end point was progression-free survival (PFS) by Response Evaluation Criteria in Solid Tumours (RECIST), version 1.1, in the intent-to-treat population.In total, 152 female patients were randomized, with 78 (51.3%) in the apatinib plus PLD group (median age, 54 years; range, 22-76 years) and 74 (48.7%) in the PLD group (median age, 56 years; range, 33-72 years). The median follow-up duration was 8.7 months (IQR, 4.7-14.1 months). The median PFS was 5.8 months (95% CI, 3.8-8.8) for treatment with apatinib plus PLD vs 3.3 months (95% CI, 2.1-3.8) for PLD (hazard ratio, 0.44; 95% CI, 0.28-0.71; P < .001). The median overall survival was 23.0 months (95% CI, 18.9 to not reached) with treatment with apatinib plus PLD vs 14.4 months (95% CI, 12.1-23.4) with PLD (hazard ratio, 0.66; 95% CI, 0.40-1.09). The most frequent grade 3 or higher treatment-emergent adverse events were decreased neutrophil counts (11 [14.9%] in the apatinib plus PLD group vs 6 [8.3%] in the PLD group), hypertension (6 [8.1%] vs none), and decreased white blood cell count (5 [6.8%] vs 3 [4.2%]). Two patients receiving treatment with apatinib plus PLD experienced grade 2 fistulas.This randomized clinical trial found that treatment with apatinib plus PLD showed promising efficacy and manageable toxic effects in patients with PROC and may be a new alternative treatment option in this setting.Clinicaltrials.gov Identifier: NCT04348032.
De novo Mutations in Domestic Cat are Consistent with an Effect of Reproductive Longevity on Both the Rate and Spectrum of Mutations
Authors: Richard J Wang, Muthuswamy Raveendran, R Alan Harris, William J Murphy, Leslie A Lyons, Jeffrey Rogers, Matthew W Hahn
Journal: Molecular Biology and Evolution (2022)

The mutation rate is a fundamental evolutionary parameter with direct and appreciable effects on the health and function of individuals. Here, we examine this important parameter in the domestic cat, a beloved companion animal as well as a valuable biomedical model. We estimate a mutation rate of 0.86 × 10-8 per bp per generation for the domestic cat (at an average parental age of 3.8 years). We find evidence for a significant paternal age effect, with more mutations transmitted by older sires. Our analyses suggest that the cat and the human have accrued similar numbers of mutations in the germline before reaching sexual maturity. The per-generation mutation rate in the cat is 28% lower than what has been observed in humans, but is consistent with the shorter generation time in the cat. Using a model of reproductive longevity, which takes into account differences in the reproductive age and time to sexual maturity, we are able to explain much of the difference in per-generation rates between species. We further apply our reproductive longevity model in a novel analysis of mutation spectra and find that the spectrum for the cat resembles the human mutation spectrum at a younger age of reproduction. Together, these results implicate changes in life-history as a driver of mutation rate evolution between species. As the first direct observation of the paternal age effect outside of rodents and primates, our results also suggest a phenomenon that may be universal among mammals.
PB2327: BONE MARROW STUDY IN THROMBOPENIA
Authors: P. López De Ugarriza, I. Hernández de Castro, A. Porro Camarero, J. C. Iglesias Lopez, G. Flórez Meana, C. Rodríguez de Miñón, A. Fonseca Mourelle, T. Arias Fernández
Journal: HemaSphere (2022)

Background: Bone marrow (BM) aspirated and biopsy are invasive procedures with potential hemorrhagic complication. In classic primary immune thrombocytopenia (ITP) guidelines it was recommended to assess the study of BM in patients older than 60 years, refractory to first-line treatment or before splenectomy. Also prior to the start thrombopoietin receptor agonists (TPO-RA) due to the occurrence of medullary fibrosis (MF). However, in more current guidelines these indications for the study of BM are not so clear. Aims: Describe the findings of BM studies performed for thrombopenia at our center. Methods: Patients with BM studies performed at our center for suspected thrombopenia between January 2017 and May 2021 were retrospectively reviewed. Both aspirates and biopsies of BM were included and those patients who had an BM study prior to the date of this review were excluded. The data obtained were analyzed using the PSPP statistical program (version 1.2.0-g0fb4db). Results: A total of 52 patients were reviewed, of which 48% were women and the age range reached was 2 – 89 years. Biopsy was only made in 23% of cases. In patients in whom only medullary aspiration was performed, 36% had thrombopenias < 30,000 x10⁹/L (considering biopsy as unsafe), 61% it was not requested and 2.5% it was not technically possible. The diagnosis of peripheral mechanism thrombopenia (PMT) occurred in 62% of cases, myelodysplastic syndrome (MDS) in 5.8%, chronic myelomonocytic leukemia (CMML) in 3.8%, and 2% of medullary aplasia, medullary fibrosis, dysplasia without MDS criteria or monoclonal gammopathy of uncertain significance, respectively. The BM study was considered normal or reactive in 10%. In both patients diagnosed with MDS and CMML, abnormalities were observed in peripheral blood smears (PBS) performed prior to the BM study, while 84% of patients diagnosed with PMT did not have atypia in the PBS reviewed. In 53% of PMT treatment with TPO-RA was initiated after the BM study. No significant bleeding complications were described in the studies conducted. Summary/Conclusion: Patients with other diagnoses than PMT already had findings in the PBS that made these diagnoses suspect. Last evidence suggests that the risk of MF of reticulin secondary to treatment with TPO-RA is low (5%) because of this, BM study before or during treatment with TPO-RA is no longer recommended. Greater consensus is needed to avoid unnecessary invasive testing for the diagnosis and follow-up of patients with ITP.
Capecitabine Maintenance in Metastatic Nasopharyngeal Carcinoma
Authors: Nithin S. G., Atul Sharma, Raja Pramanik
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Mitochondrial dysfunction in cell senescence and aging
Authors: Satomi Miwa, Sonu Kashyap, Eduardo Chini, Thomas von Zglinicki
Journal: Journal of Clinical Investigation (2022)

Mitochondrial dysfunction and cell senescence are hallmarks of aging and are closely interconnected. Mitochondrial dysfunction, operationally defined as a decreased respiratory capacity per mitochondrion together with a decreased mitochondrial membrane potential, typically accompanied by increased production of oxygen free radicals, is a cause and a consequence of cellular senescence and figures prominently in multiple feedback loops that induce and maintain the senescent phenotype. Here, we summarize pathways that cause mitochondrial dysfunction in senescence and aging and discuss the major consequences of mitochondrial dysfunction and how these consequences contribute to senescence and aging. We also highlight the potential of senescence-associated mitochondrial dysfunction as an antiaging and antisenescence intervention target, proposing the combination of multiple interventions converging onto mitochondrial dysfunction as novel, potent senolytics.
RNF213-associated urticarial lesions with hypercytokinemia
Authors: Camille Louvrier, Fawaz Awad, Anne Cosnes, Elma El Khouri, Eman Assrawi, Aphrodite Daskalopoulou, Bruno Copin, Hélène Bocquet, Sandra Chantot Bastaraud, Angela Arenas Garcia, Florence Dastot Le Moal, Pierre De La Grange, Philippe Duquesnoy, Chiara I. Guerrera, William Piterboth, Nicolas Ortonne, Olivier Chosidow, Sonia A. Karabina, Serge Amselem, Irina Giurgea
Journal: Journal of Allergy and Clinical Immunology (2022)
CircEZH2/miR-133b/IGF2BP2 aggravates colorectal cancer progression via enhancing the stability of m6A-modified CREB1 mRNA
Authors: Bing Yao, Qinglin Zhang, Zhou Yang, Fangmei An, He Nie, Hui Wang, Cheng Yang, Jing Sun, Ke Chen, Jingwan Zhou, Bing Bai, Shouyong Gu, Wei Zhao, Qiang Zhan
Journal: Molecular Cancer (2022)

Abstract Background Aberrant expression of circular RNAs (circRNAs) contributes to the initiation and progression of human malignancies, but the underlying mechanisms remain largely elusive. Methods High-throughput sequencing was performed to screen aberrantly expressed circRNAs or miRNAs in colorectal cancer (CRC) and adjacent normal tissues. A series of gain- and loss-of-function studies were conducted to evaluate the biological behaviors of CRC cells. RNA pulldown, mass spectrometry, RIP, qRT-PCR, Western blot, luciferase reporter assays and MeRIP-seq analysis were further applied to dissect the detailed mechanisms. Results Here, a novel circRNA named circEZH2 (hsa_circ_0006357) was screened out by RNA-seq in CRC tissues, whose expression is closely related to the clinicpathological characteristics and prognosis of CRC patients. Biologically, circEZH2 facilitates the proliferation and migration of CRC cells in vitro and in vivo. Mechanistically, circEZH2 interacts with m 6 A reader IGF2BP2 and blocks its ubiquitination-dependent degradation. Meanwhile, circEZH2 could serve as a sponge of miR-133b, resulting in the upregulation of IGF2BP2. Particularly, circEZH2/IGF2BP2 enhances the stability of CREB1 mRNA, thus aggravating CRC progression. Conclusions Our findings not only reveal the pivotal roles of circEZH2 in modulating CRC progression, but also advocate for attenuating circEZH2/miR-133b/IGF2BP2/ CREB1 regulatory axis to combat CRC.
Brush cells fine-tune neurogenic inflammation in the airways
Authors: Qihua Ye, Lora G. Bankova
Journal: Journal of Clinical Investigation (2022)

Airway epithelial cells, once considered a simple barrier layer, are now recognized as providing an active site for antigen sensing and immune response initiation. Most mucosal sites contain chemosensory epithelial cells, rare and specialized cells gaining recognition for their unique functions in sensing and directing the immune response symphony. In this issue of the JCI, Hollenhorst, Nandigama, et al. demonstrated that tracheal chemosensory brush cells detected bitter-tasting substances, including quorum-sensing molecules (QSMs) generated by pathogenic Pseudomonas aeruginosa. The authors used various techniques, including genetic deletion of brush cells, genetic manipulation of brush cell signaling, deletion of sensory neurons, in vivo imaging, and infection models with P. aeruginosa, to show that QSMs increased vascular permeability and innate immune cell influx into the trachea. These findings link the recognition of bacterial QSMs to the innate immune response in the airways, with translational implications for airway inflammation and infectious pathology.
Glycoengineered anti-CD39 promotes anticancer responses by depleting suppressive cells and inhibiting angiogenesis in tumor models
Authors: Haohai Zhang, Lili Feng, Paola de Andrade Mello, Changchuin Mao, Richard Near, Eva Csizmadia, Leo Li-Ying Chan, Keiichi Enjyoji, Wenda Gao, Haitao Zhao, Simon C. Robson
Journal: Journal of Clinical Investigation (2022)

Immunosuppressive cells accumulating in the tumor microenvironment constitute a formidable barrier that interferes with current immunotherapeutic approaches. A unifying feature of these tumor-associated immune and vascular endothelial cells appears to be the elevated expression of ectonucleotidase CD39, which in tandem with ecto-5′-nucleotidase CD73, catalyzes the conversion of extracellular ATP into adenosine. We glycoengineered an afucosylated anti-CD39 IgG2c and tested this reagent in mouse melanoma and colorectal tumor models. We identified major biological effects of this approach on cancer growth, associated with depletion of immunosuppressive cells, mediated through enhanced Fcγ receptor–directed (FcγR-directed), antibody-dependent cellular cytotoxicity (ADCC). Furthermore, regulatory/exhausted T cells lost CD39 expression, as a consequence of antibody-mediated trogocytosis. Most strikingly, tumor-associated macrophages and endothelial cells with high CD39 expression were effectively depleted following antibody treatment, thereby blocking angiogenesis. Tumor site–specific cellular modulation and lack of angiogenesis synergized with chemotherapy and anti–PD-L1 immunotherapy in experimental tumor models. We conclude that depleting suppressive cells and targeting tumor vasculature, through administration of afucosylated anti-CD39 antibody and the activation of ADCC, comprises an improved, purinergic system–modulating strategy for cancer therapy.
For-profit health care might be damaging population health
Authors: Andrew Street
Journal: The Lancet Public Health (2022)

Arguments have long raged about what role the private sector should play in the UK's health system, where provision is dominated by the National Health Service (NHS). There has always been some level of mixed public–private provision in UK health care, with more than 500 private hospitals currently in the UK,1 many senior NHS doctors also working in a private capacity,2 and general practices being privately owned.
PB2248: CONCOMITANT HEREDITARY SPHEROCYTOSIS AND PYRUVATE KINASE DEFICIENCY IN A SPANISH FAMILY WITH CHRONIC HEMOLYTIC ANEMIA. CONTRIBUTION OF LASER EKTACYTOMETRY TO CLINICAL DIAGNOSIS
Authors: J.-L. Vives Corrons, E. Krishnevskaya, L. Montllor, V. Leguizamón, M. Garcia Bernal
Journal: HemaSphere (2022)

Background: Hereditary Spherocytosis (HS) and Pyruvate Kinase deficiency (PKD) are the most common causes of hereditary chronic hemolytic anemia. Here we describe clinical and genetic characteristics of a Spanish family with concomitant b-spectrin (SPTB) c.647G>A variant and pyruvate kinase (PKLR) c.1706G>A variant Aims: The objective of our study is to evaluate the possible modulator effect of Pyruvate Kinase deficiency (PKD) on the clinical expression of Hereditary Spheroctosis (HS) in a Spansh family with coinheritance of HS and PKD Methods: Hematological investigation, hemolysis tests and specific red cells studies were performed in a family of 11 members according to conventional procedures.The ektacytometric study was performed using the osmoscan module of the Lorca ektacytometer (MaxSis. RR Mechatronics). The presence of the SPTB and PKLR variants was confirmed by t-NGS Results: The t-NGS genetic characterization of the 11 family members showed the presence of a heterozygous mutation for the b-spectrin (SPTB; c.647G>A) in 7 members with HS, 3 of them co-inherited the PKLR variant c.1706G>A. In the remaining 4 members, no gene mutation was found. (FIGURE) Ektacytometry allowed a clear diagnostic orientation of HS, independently from the PKLR variant Image:Summary/Conclusion: This family study allows to conclude that the SPTB mutation, (c.647G>A) previously described as Likely Pathogenic (LP), has to be classified as Pathogenic (P) according to the HGVS variation nomenclature. In addition, after the 6 years of clinical follow-up of the patients with HS it can infer that the chronic hemolytic anemia may be attributable to the SPTB mutation only, without influence of the concomitant PKLR. Moreover, only the family members with the SPTB mutation exhibited an ektacytometric profile characteristic of HS
Perioperative Stroke Risk Model—One Size Fits All?
Authors: Stephen A. Esper, Parthasarathy D. Thirumala, Danny Chu
Journal: JAMA Surgery (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Consensus-Based Guidance on Opioid Management in Individuals With Advanced Cancer-Related Pain and Opioid Misuse or Use Disorder
Authors: Katie Fitzgerald Jones, Dmitry Khodyakov, Robert Arnold, Hailey Bulls, Emily Dao, Jennifer Kapo, Diane Meier, Judith Paice, Jane Liebschutz, Christine Ritchie, Jessica Merlin
Journal: JAMA Oncology (2022)

Importance Opioid misuse and opioid use disorder (OUD) are important comorbidities in people with advanced cancer and cancer-related pain, but there is a lack of consensus on treatment. Objective To develop consensus among palliative care and addiction specialists on the appropriateness of various opioid management strategies in individuals with advanced cancer-related pain and opioid misuse or OUD. Design, Setting, and Participants For this qualitative study, using ExpertLens, an online platform and methodology for conducting modified Delphi panels, between August and October 2020, we conducted 2 modified Delphi panels to understand the perspectives of palliative and addiction clinicians on 3 common clinical scenarios varying by prognosis (weeks to months vs months to years). Of the 129 invited palliative or addiction medicine specialists, 120 participated in at least 1 round. A total of 84 participated in all 3 rounds. Main Outcomes and Measures Consensus was investigated for 3 clinical scenarios: (1) a patient with a history of an untreated opioid use disorder, (2) a patient taking more opioid than prescribed, and (3) a patient using nonprescribed benzodiazepines. Results Participants were mostly women (47 [62%]), White (94 (78 [65%]), and held MD/DO degrees (115 [96%]). For a patient with untreated OUD, regardless of prognosis, it was deemed appropriate to begin treatment with buprenorphine/naloxone and inappropriate to refer to a methadone clinic. Beginning split-dose methadone was deemed appropriate for patients with shorter prognoses and of uncertain appropriateness for those with longer prognoses. Beginning a full opioid agonist was deemed of uncertain appropriateness for those with a short prognosis and inappropriate for those with a longer prognosis. Regardless of prognosis, for a patient with no medical history of OUD taking more opioids than prescribed, it was deemed appropriate to increase monitoring, inappropriate to taper opioids, and of uncertain appropriateness to increase the patient’s opioids or transition to buprenorphine/naloxone. For a patient with a urine drug test positive for non-prescribed benzodiazepines, regardless of prognosis, it was deemed appropriate to increase monitoring, inappropriate to taper opioids and prescribe buprenorphine/naloxone. Conclusions and Relevance The findings of this qualitative study provide urgently needed consensus-based guidance for clinicians and highlight critical research and policy gaps.
Managing Cancer Pain in Patients With Opioid Use Disorder or Nonmedical Opioid Use
Authors: Joseph Arthur, Eduardo Bruera
Journal: JAMA Oncology (2022)

In this issue of JAMA Oncology, Fitzgerald Jones et al1 publish the results of a Delphi consensus panel on the management of pain in patients with advanced cancer in the context of opioid use disorder or nonmedical opioid use.